Otolaryngology Commons^™

Influence Of Oral Microbiome On Longitudinal Patterns Of Oral Mucositis Severity In Patients With Squamous Cell Carcinoma Of The Head And Neck, Liangliang Zhang, Erin Marie D San Valentin, Teny M John, Robert R Jenq, Kim-Anh Do, Ehab Y Hanna, Christine B Peterson, Cielito C Reyes-Gibby

Faculty, Staff and Student Publications

Background: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck.

Methods: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit …

Outcomes Of Treatment With Neoadjuvant Cemiplimab For Patients With Advanced, Resectable Cutaneous Squamous Cell Carcinoma Of The Head And Neck: Secondary Analysis Of A Phase 2 Clinical Trial, Renata Ferrarotto, Priyadharsini Nagarajan, Jacob M Maronge, Jason M Johnson, David I Rosenthal, Jeffrey N Myers, Neil D Gross

Faculty, Staff and Student Publications

This secondary analysis of a phase 2 clinical trial examines long-term survival for resectable cutaneous squamous cell carcinoma of the head and neck according to pathologic response.

Machine Learning Driven Index Of Tumor Multinucleation Correlates With Survival And Suppressed Anti-Tumor Immunity In Head And Neck Squamous Cell Carcinoma Patients, Can F Koyuncu, Mitchell J Frederick, Lester D R Thompson, Germán Corredor, Sirvan Khalighi, Zelin Zhang, Bolin Song, Cheng Lu, Reetoja Nag, Vidya Sankar Viswanathan, Michael Gilkey, Kailin Yang, Shlomo A Koyfman, Deborah J Chute, Patricia Castro, James S Lewis, Anant Madabhushi, Vlad C Sandulache

Faculty, Staff and Students Publications

OBJECTIVES: Matching treatment intensity to tumor biology is critical to precision oncology for head and neck squamous cell carcinoma (HNSCC) patients. We sought to identify biological features of tumor cell multinucleation, previously shown by us to correlate with survival in oropharyngeal (OP) SCC using a machine learning approach.

MATERIALS AND METHODS: Hematoxylin and eosin images from an institutional OPSCC cohort formed the training set (D

RESULTS: MuNI correlated with overall survival. A multivariable nomogram that included MuNI, age, race, sex, T/N stage, and smoking status yielded a C-index of 0.65, and MuNI was prognostic of overall survival (2.25, 1.07-4.71, 0.03), …

Immunogenetic Determinants Of Susceptibility To Head And Neck Cancer In The Million Veteran Program Cohort, Yanhong Liu, Jennifer R Kramer, Vlad C Sandulache, Robert Yu, Guojun Li, Liang Chen, Zenab I Yusuf, Yunling Shi, Saiju Pyarajan, Spyros Tsavachidis, Li Jiao, Michelle L Mierzwa, Elizabeth Chiao, Yvonne M Mowery, Andrew Shuman, Sanjay Shete, Andrew G Sikora, Donna L White

Faculty, Staff and Student Publications

Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and …

Role Of Sentinel Lymph Node Biopsy For Oral Squamous Cell Carcinoma: Current Evidence And Future Challenges, Sophie S Jang, Morgan E Davis, David R Vera, Stephen Y Lai, Theresa W Guo

Faculty, Staff and Student Publications

Sentinel lymph node biopsy (SLNB) has been used across oncological specialties for prognostication, staging, and identification of occult nodal metastasis. Recent studies demonstrated the potential clinical utility of SLNB in oral cavity squamous cell carcinoma (OCSCC). Elective neck dissection is the current standard of care in early management of OCSCC with depth of invasion greater than 2-4 mm; however, majority of patients ultimately do not have nodal disease on final pathology. SLNB is an alternative procedure widely adopted in early cancer management in many oncological subspecialities. Several considerations such as depth of invasion, nodal mapping, histopathology methods, operator variability, postoperative …

Feasibility Of Clinical Evaluation Of Individuals With Increased Risk For Hpv-Associated Oropharynx Cancer, Nicholas Scott-Wittenborn, Gypsyamber D'Souza, Nafi Aygun, Sakshi R Tewari, Javad Azadi, Peter Vosler, Zhen Gooi, Vikas Mehta, Wojciech Mydlarz, Melonie Nance, Stefan Mlot, Mihir R Patel, Marietta Tan, Brett A Miles, Tanya Troy, Carole Fakhry

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus-associated oropharynx squamous cell carcinoma (HPV-OPSCC) has no known pre-malignant lesion. While vaccination offers future primary prevention, there is current interest in secondary prevention. The feasibility of clinical evaluation of individuals at increased risk for HPV-OPSCC is unclear.

METHODS: Individuals with risk factors for HPV-OPSCC were enrolled in a prospective study (MOUTH). Participants positive for biomarkers associated with HPV-OPSCC were eligible for a clinical evaluation which comprised a head and neck examination and imaging with ultrasound and/or magnetic resonance imaging (MRI). This study was designed to evaluate feasibility of clinical evaluation in a screening study.

RESULTS: Three hundred …

Chemoradiation Therapy Alters The Pd-L1 Score In Locoregional Recurrent Squamous Cell Carcinomas Of The Head And Neck, Brian J Park, Austin K Mattox, Daniel Clayburgh, Mihir Patel, R Bryan Bell, Bevan Yueh, Rom Leidner, Hong Xiao, Marcus Couey, Shiting Li, Tingting Qin, Maureen A Sartor, Belinda Cairns, Tracy Macdonough, Kyle Halliwill, Daniel Deschler, Derrick T Lin, William C Faquin, Peter M Sadow, Sara I Pai

Faculty, Staff and Student Publications

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did …

Risk And Incidence Of Head And Neck Cancers In Veterans Living With Hiv And Matched Hiv-Negative Veterans, Angela L Mazul, Christine M Hartman, Yvonne M Mowery, Jennifer R Kramer, Donna L White, Kathryn E Royse, Suchismita Raychaudhury, Vlad C Sandulache, Sarah T Ahmed, Jose P Zevallos, Peter A Richardson, Andrew G Sikora, Elizabeth Y Chiao

Faculty, Staff and Students Publications

BACKGROUND: Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study.

METHODS: The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic …

Swallowing After Primary Tors And Unilateral Or Bilateral Radiation For Low- To Intermediate-Risk Tonsil Cancer, Carly E A Barbon, Christopher M K Yao, Christine B Peterson, Amy C Moreno, Ryan P Goepfert, Faye M Johnson, Gregory M Chronowski, Clifton D Fuller, Neil D Gross, Katherine A Hutcheson

Faculty, Staff and Student Publications

Objective: The primary course of treatment for patients with low- to intermediate-risk tonsil cancer has evolved with a shift toward primary transoral robotic surgery (TORS) or radiation therapy (RT). While favorable outcomes have been reported after deintensification via unilateral TORS or RT (uniRT), comparisons of functional outcomes between these treatments are lacking. We compared clinical outcomes (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST] and feeding tube [FT]) and patient-reported swallowing outcomes (MD Anderson Dysphagia Inventory [MDADI]) based on primary treatment strategy: TORS, uniRT, or bilateral RT (biRT).

Study design: Secondary analysis of prospective cohort.

Setting: Single institution.

Methods: The study …

Changes In Apparent Diffusion Coefficient (Adc) In Serial Weekly Mri During Radiotherapy In Patients With Head And Neck Cancer: Results From The Predict-Hn Study, Sweet Ping Ng, Carlos E Cardenas, Houda Bahig, Baher Elgohari, Jihong Wang, Jason M Johnson, Amy C Moreno, Shalin J Shah, Adam S Garden, Jack Phan, G Brandon Gunn, Steven J Frank, Yao Ding, Lumine Na, Ying Yuan, Diana Urbauer, Abdallah S R Mohamed, David I Rosenthal, William H Morrison, Michael P Macmanus, Clifton D Fuller

Faculty, Staff and Student Publications

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy.

Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time.

Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that …

A Nanoengineered Topical Transmucosal Cisplatin Delivery System Induces Anti-Tumor Response In Animal Models And Patients With Oral Cancer, Manijeh Goldberg, Aaron Manzi, Amritpreet Birdi, Brandon Laporte, Peter Conway, Stefanie Cantin, Vasudha Mishra, Alka Singh, Alexander T Pearson, Eric R Goldberg, Sam Goldberger, Benjamin Flaum, Rifat Hasina, Nyall R London, Gary L Gallia, Chetan Bettegowda, Simon Young, Vlad Sandulache, James Melville, Jonathan Shum, Sonya E O'Neill, Erkin Aydin, Alex Zhavoronkov, Anxo Vidal, Atenea Soto, Maria Jose Alonso, Ari J Rosenberg, Mark W Lingen, Anil D'Cruz, Nishant Agrawal, Evgeny Izumchenko

Faculty, Staff and Students Publications

Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor …

Genetic Variants In Cyp2b6 And Hsd17b12 Associated With Risk Of Squamous Cell Carcinoma Of The Head And Neck, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Kristina R Dahlstrom, Mulong Du, Christopher I Amos, David C Christiani, Philip Lazarus, Qingyi Wei

Faculty, Staff and Students Publications

Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10

Detection Accuracy Of The Cobas Hpv Assay For High-Risk Hpv In Head And Neck Fna Biopsy Specimens, Ming Guo, Abha Khanna, Agata A Tinnirello, Jessica Hwang, Ping Zhang, Li Xu, Guojun Li, Kristina R Dahlstrom, Erich M Sturgis, John Stewart

Faculty, Staff and Students Publications

BACKGROUND: This study evaluated the detection accuracy of the Cobas human papillomavirus (HPV) assay for high-risk human papillomavirus (hrHPV) and HPV-16 in head and neck fine-needle aspiration (FNA) specimens with squamous cell carcinoma.

METHODS: Head and neck FNA biopsy specimens from 2012 to 2020 were retrospectively collected. Cobas HPV testing was performed on 90 FNA specimens with valid Cervista HPV testing results. Results of Cobas HPV and Cervista HPV assays were compared. A Linear Array or SPF10-LiPA25 HPV genotyping assay resolved cases with discrepant results. The κ value and accuracy of Cobas HPV testing were calculated. The accuracy of the …

P16 Represses Dna Damage Repair Via A /Novel Ubiquitin-Dependent Signaling Cascade, David P Molkentine, Jessica M Molkentine, Kathleen A Bridges, David R Valdecanas, Annika Dhawan, Reshub Bahri, Andrew J Hefner, Manish Kumar, Liangpeng Yang, Mohamed Abdelhakiem, Phillip M Pifer, Vlad Sandulache, Aakash Sheth, Beth M Beadle, Howard D Thames, Kathryn A Mason, Curtis R Pickering, Raymond E Meyn, Heath D Skinner

Faculty, Staff and Students Publications

Squamous cell carcinoma driven by human papillomavirus (HPV) is more sensitive to DNA-damaging therapies than its HPV-negative counterpart. Here, we show that p16, the clinically used surrogate for HPV positivity, renders cells more sensitive to radiotherapy via a ubiquitin-dependent signaling pathway, linking high levels of this protein to increased activity of the transcription factor SP1, increased HUWE1 transcription, and degradation of ubiquitin-specific protease 7 (USP7) and TRIP12. Activation of this pathway in HPV-positive disease led to decreased homologous recombination and improved response to radiotherapy, a phenomenon that can be recapitulated in HPV-negative disease using USP7 inhibitors in clinical development. This …

Outcomes Of Venous End-To-Side Microvascular Anastomoses Of The Head And Neck., Matthew Stewart, Perry Hammond, Ishani Khatiwala, Brian Swendseid, Farshid Taghizadeh, Daniel Petrisor, Tingting Zhan, Richard Goldman, Adam Luginbuhl, Ryan Heffelfinger, Larissa Sweeny, Mark K Wax, Joseph M. Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: The literature on outcomes of end-to-side (ETS) anastomoses for microvascular reconstruction of the head and neck is limited. This series reviews ETS in free tissue transfer (FTT) across multiple institutions to better understand their usage and associated outcomes.

STUDY DESIGN: Retrospective review of 2482 consecutive patients across three tertiary institutions.

METHODS: Adult patients (> 18) who received a FTT from 2006 to 2019 were included.

RESULTS: Two hundred and twenty-one FTT were identified as requiring at least one ETS anastomosis. These ETS cases had a failure rate of 11.2% in comparison to 3.8% in a cohort of end-to-end (ETE) …

Early Adoption Of Transoral Robotic Surgical Program: Preliminary Outcomes., David Cognetti, Adam Luginbuhl, Anthony L. Nguyen, Joseph Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: The objective of this study is to demonstrate the feasibility and safety of establishing a transoral robotic surgical (TORS) program in the post-Food and Drug Administration (FDA) approval setting. Early outcomes are compared with the previously reported results of pioneering centers.

STUDY DESIGN: Clinical data from a prospective TORS study.

SETTING: Academic university institution.

SUBJECTS AND METHODS: Sixty-one patients treated with 63 TORS procedures. Main outcome measures: intraoperative times, margin status, complications, time to diet, and percutaneous endoscopic gastrostomy (PEG) tube retention rate. The authors also report oncologic outcomes on their first 30 patients.

RESULTS: The spectrum of subsites …