Otolaryngology - Head and Neck Surgery Research

HPV-Oropharyngeal Related Cancer Screening

Our research team is dedicated to enhancing the early detection of HPV (Human Papillomavirus) related oropharyngeal cancers. We focus exclusively on implementing novel blood, saliva, and urine biomarkers for HPV-related cancers and optimizing screening methods to identify these cancers at the earliest, most treatable stages. By prioritizing effective screening strategies, we aim to improve patient survival and functional outcomes and contribute to the broader fight against HPV-related cancers. Our efforts are supported by competitive funding from the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and non-profit foundations.

Why HPV-Related Related Cancer Screening Matters

HPV (Human Papillomavirus) is the primary cause of oropharyngeal cancer (part of the throat, specifically the tonsils and base of the tongue).  Oropharyngeal cancer is now the number one HPV-related cancer in the U.S., surpassing cervical cancer in the last decade. The national rate of these cancers has been increasing dramatically since the mid-1990s, particularly among men. Cancer screening and early detection will be essential to detect these cancers earlier and to provide effective and less extensive treatment, ultimately saving lives and reducing the disease burden on individual patients. If you qualify for one of our studies, we hope you will join us in advancing screening innovations to improve early detection and treatment outcomes for those affected by HPV-related oropharyngeal cancer.

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Previous Studies: Key Findings

Our team has conducted the TRINITY study in Houston and Dallas, successfully identifying a small group of 25 middle-aged men at extreme risk for HPV-related oropharyngeal cancer out of approximately 1,600 men who enrolled. Thus far, an early HPV-related oropharyngeal cancer has been detected in 2 of these 25 men.
Building on the success of this initial trial, we are now conducting a larger study involving over 1,000 men and women aged 45-69 years across Texas. This study employs a convenient approach, allowing participants to provide blood, saliva, and urine samples at a location near their home, with remote processing conducted in Houston. Participants who test positive (estimated to be less than 3% of those tested) are invited to Houston for detailed in-person examinations, funded by the study.

Quality Outcomes and Measures for Microvascular Free Tissue Transfer of the Head and Neck

The treatment of head, neck, and skin cancers often involves extensive surgeries that can lead to significant disabilities, including impaired swallowing, cosmetic deformities, and loss of voice. Use of complex reconstructive modalities such as microvascular free tissue transfer has afforded surgeons the ability to restore a patient’s form and function (jawbone, skin, throat), improving quality of life and therapeutic potential. Our reconstructive team is a high-volume microvascular free tissue transfer center and has worked extensively locally and nationally to analyze functional outcomes, devise novel surgical techniques, and establish metrics to measure quality following these intensive procedures.

Recent Publications:

Wang R, Horwich P, Sandulache VC, Hernandez DJ, Hornig J, Graboyes EM, Liou NE, Skoner J, Haskins AD, Ranasinghe V, Day TA, Sturgis EM, Huang AT. Safety of microvascular free tissue transfer reconstruction of the head and neck in the setting of chronic pharmacologic immunosuppression. Head Neck. 2022 Jul;44(7):1520-1527. 

Shum J, Manon V, Huang A. A combined transoral and contralateral submandibular approach in the surgical management of osteoradionecrosis of the mandible with free flap reconstruction. J Oral Maxillofac Surg. 2022 Sep;80(9):1544-1549.

Macias D, Hand BN, Pipkorn P, Williams AM, Chang SS, Zenga J, Nilsen ML, Rhoten BA, Huang AT, Osazuwa-Peters N, Maurer S, Balliet W, Li H, Ruggiero KJ, Sterba KR, Graboyes EM. Association of Inventory to Measure and Assess imaGe Disturbance – Head and Neck Scores with Clinically Meaningful Body Image-Related Distress Among Head and Neck Cancer Survivors. Front Psychol. 2021 Dec 10;12:794038. doi:10.3389/fpsyg.2021.794038. eCollection 2021.

Macias D, Hand BN, Maurer S, Balliet W, Ellis MA, Pipkorn P, Huang AT, Nilsen ML, Ruggiero KJ, Williams AM, Marsh CH, Li H, Rhoten BA, Sterba KR, Graboyes EM. Factors Associated with Risk of Body Image-Related Distress in Patients with Head and Neck Cancer. JAMA Otolaryngology Head Neck Surg. 2021 Dec 1;147(12):1019-1026.

Shi J, Ayeni T, Gallagher KK, Patel AJ, Jalali A, Hernandez DJ, Haskins AD, Sandulache VC, Sturgis EM, Huang AT. Reconstructive outcomes of multilayered closure of large skull base dural defects following open anterior craniofacial resection. Journal of Neurological Surgery Part B: Skull Base. 2021 Feb 22;83(4):359-366.

Mays AC, Yarlagadda B, Achim V, Jackson R, Pipkorn P, Huang AT, Rajasekaran K, Sridharan S, Rosko AJ, Orosco RK, Coughlin AM, Wax MK, Shnayder Y, Spanos WC, Farwell DG, McDaniel LS, Hanasono MM. Examining the relationship of immunotherapy and wound complications following flap reconstruction in patients with head and neck cancer. Head Neck. 2021 May;43(5):1509-1520.

Sheehan CC, Haskins AD, Huang AT, Hernandez DJ. Cephalometric and functional mandibular reconstructive outcomes using a horizontal scapular tip free flap. Otolaryngology Head Neck Surg. 2021 Sep;165(3):414-418.

Harris BN, Ghazizadeh S, Bayon R, Kejner AE, Cannady SB, Greene BJ, Huang AT, Curry J, Blackwell KE, Ducic Y, Wax MK.  Safety of fibula free flap in patients following total knee replacement. Head Neck. 2021 Feb;43(2):585-589.

Hudson CS, Huang AT. Perforator-based propeller flaps for reconstruction of massive anterolateral thigh donor site wounds. Head Neck. 2020 Dec;42(12):E49-E52.

Chen DW, Ellis MA, Horwich P, Sandulache VC, Liou NE, Hernandez DJ, Sturgis EM, Graboyes EM, Hornig JD, Day TA, Huang AT. Free flap inset techniques in salvage laryngopharyngectomy repair: impact on fistula formation and function. Laryngoscope. 2021 Mar;131(3):E875-E881.

Graboyes EM, Hand BN, Ellis MA, Huang AT, Nilsen ML, Pipkorn P, Marsh CH, Maurer S, Day TA, Sterba KR. Validation of a novel, multi-domain head and neck cancer- and function-distress patient-reported outcome measure. Otolaryngology Head Neck Surgery. 2020 Nov;163(5):979-985.

Fancy T, Huang AT, Kass JI, Lamarre ED, Tassone P, Mantravadi AV, Alwani MM, Subbarayan RS, Bur AM, Worley ML, Graboyes EM, McMullen CP, Azoulay O, Wax MK, Cave TB, Al-Khudari S, Abello EH, Higgins KM, Ryan JT, Orzell SC, Goldman RA, Vimawala S, Fernandes RP, Abdelmalik M, Rajasekaran K, L’Esperance HE, Kallogjeri D, Rich JT. Complications, mortality, and functional decline in patients 80 years and older undergoing major head and neck ablation and reconstruction – a multi-institutional cohort study. JAMA Otolaryngology – Head & Neck Surgery. 2019 Oct 10;145(12):1150-7.

Kansara S, Wang T, Koochakzadeh S, Liou NE, Graboyes EM, Skoner JM, Hornig JD, Sandulache VC, Day TA, Huang AT. Prognostic factors associated with achieving total oral diet following osteocutaneous microvascular free tissue transfer reconstruction of the oral cavity. Oral Oncology. 2019 Nov;98:1-7.

Chen DW, Wang T, Shey-Sen Ni J, Sandulache VC, Graboyes EM, Worley M, Hornig JD, Skoner JM, Day TA, Huang AT. Prognostic factors associated with achieving total oral diet after glossectomy with microvascular free tissue transfer reconstruction. Oral Oncology. 2019;92:59-66.

Investigators in the Baylor College of Medicine Hearing and Balance Center study the intersection of hearing loss pathophysiology and natural history, along with surgical and medical means used to rehabilitate hearing loss.  

Active research projects are focused on optimal delivery of rehabilitative care through innovative approaches and improved care paradigms developed in a multidisciplinary manner with collaborators from BCM and other TMC institutions such as the University of Houston and Rice University.

Recent Publications: 

McMillan RA, Nassiri AM, Leonel LC, Rezende NC, Peris Celda M, Sweeney AD, Carlson ML. The posterior ligament of the incus (“white dot”): A reliable surgical landmark for the facial recess.  American Journal of Otolaryngology. 2022. 43(2): 103304.  PMID 34896938.

Gadot R, Anand A, Lovin BD, Sweeney AD, Patel AJ. Predicting Surgical Decision Making in Vestibular Schwannoma using Tree-Based Machine Learning.  Neurosurgical Focus.  2022. 52(4): E8. PMID 35364585. 

You P, Lovin, BD, Patel AJ, Hosek KE, Peng A, Sweeney AD.  Quality of life after modified-Rambo ear canal closure in pediatric and adult patients.  Otolaryngology – Head and Neck Surgery. Online ahead of print. 4/2022. PMID 35414323 

Choi JS, Sweeney AD, Alava I, Lovin BD, Lindquist NR, Appelbaum EN, Vrabec JT.  Otosclerosis in an Urban Population. Otology & Neurotology. 2021. 42(1):  24-29.  PMID 33201078. 

Breen JT, Sweeney AD, Vrabec JT. The Potential for Preserved Cochleovestibular Function in the Setting of Prolonged Pneumolabyrinth.  Otology & Neurotology.  2020. 41(7): 929-933. PMID 32558757.

Pattisapu P, Lindquist NR, Appelbaum EN, Silva RC, Vrabec JT, Sweeney AD.  A systematic review of cochlear implant outcomes in prelingually-deafened, late-implanted patients.  Otology & Neurotology. 2020. 41(4): 444-451. PMID 32176122.

Marinelli JP, Marvisi C, Vaglio A, Peters PA, Dowling EM, Palumbo A, Lane JI, Appelbaum EN, Sweeney AD, Carlson ML.  Manifestations of Skull Base IgG4-Related Disease: A Multi-Institutional Study. The Laryngoscope.  2020. 130(11)L: 2574-2580. PMID 31841234.

Abnormal metabolism was described as a hallmark of cancer over a half century ago. Over the last decade, in collaboration with our colleagues at the University of Texas MD Anderson Cancer Center, we have shown that differential energetic and REDOX regenerative pathways accompany the development of head and neck cancer and contribute to conventional chemotherapy and radiation resistance as well as suppressed antitumor immunity. Active research efforts are focused on identification of novel metabolic vulnerabilities which are targetable in head and neck cancers through a combination of basic science and translational approaches, coupled with clinical trial development and implementation.

Recent Publications: 

Ahmed KM, Veeramachaneni R, Deng D, Putluri N, Putluri V, Cardenas MF, Wheeler DA, Decker WK, Frederick AI, Kazi S, Sikora AG, Sandulache VC, Frederick MJ. Glutathione peroxidase 2 is a metabolic driver of the tumor immune microenvironment and immune checkpoint inhibitor response. J Immunother Cancer. 2022 Aug;10(8):e004752.

Veeramachaneni R, Yu W, Newton JM, Kemnade JO, Skinner HD, Sikora AG, Sandulache VC. Metformin generates profound alterations in systemic and tumor immunity with associated antitumor effects. J Immunother Cancer. 2021 Jul;9(7):e002773.

Chen Y, Maniakas A, Tan L, Cui M, Le X, Niedzielski JS, Michel KA, Harlan CJ, Lu W, Henderson YC, Mohamed ASR, Lorenzi PL, Putluri N, Bankson JA, Sandulache VC, Lai SY. Development of a rational strategy for integration of lactate dehydrogenase A suppression into therapeutic algorithms for head and neck cancer. Br J Cancer. 2021 May;124(10):1670-1679. 

Yu W, Chen Y, Putluri N, Coarfa C, Robertson MJ, Putluri V, Stossi F, Dubrulle J, Mancini MA, Pang JC, Nguyen T, Baluya D, Myers JN, Lai SY, Sandulache VC. Acquisition of Cisplatin Resistance Shifts Head and Neck Squamous Cell Carcinoma Metabolism toward Neutralization of Oxidative Stress. Cancers (Basel). 2020 Jun 24;12(6):1670. 

Frederick M, Skinner HD, Kazi SA, Sikora AG, Sandulache VC. High expression of oxidative phosphorylation genes predicts improved survival in squamous cell carcinomas of the head and neck and lung. Sci Rep. 2020 Apr 14;10(1):6380.

Matching treatment intensity to disease biology is critical to achieving a high therapeutic index which maximizes oncologic control and minimizes normal tissue toxicity. Our investigators utilize conventional (genomic, transcriptomic, proteomic) and novel radiomic and pathomic biomarkers of disease aggressiveness and treatment responsiveness to risk-stratify head and neck cancer patients prior to treatment initiation. These static risk-stratification approaches are augmented by the deployment of state-of-the-art metabolic imaging platforms which can interrogate treatment response in real-time in order to develop adaptive, individualized risk stratification profiles for patients with head and neck cancer.

Recent Publications:

Sandulache VC, Chen Y, Feng L, William WN, Skinner HD, Myers JN, Meyn RE, Li J, Mijiti A, Bankson JA, Fuller CD, Konopleva MY, Lai SY. Metabolic interrogation as a tool to optimize chemotherapeutic regimens. Oncotarget. 2017 Mar 14;8(11):18154-18165. 

Sandulache VC, Chen Y, Skinner HD, Lu T, Feng L, Court LE, Myers JN, Meyn RE, Fuller CD, Bankson JA, Lai SY. Acute Tumor Lactate Perturbations as a Biomarker of Genotoxic Stress: Development of a Biochemical Model. Mol Cancer Ther. 2015 Dec;14(12):2901-8. 

Corredor G, Toro P, Koyuncu C, Lu C, Buzzy C, Bera K, Fu P, Mehrad M, Ely KA, Mokhtari M, Yang K, Chute D, Adelstein DJ, Thompson LDR, Bishop JA, Faraji F, Thorstad W, Castro P, Sandulache V, Koyfman SA, Lewis JS, Madabhushi A. An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer. J Natl Cancer Inst. 2022 Apr 11;114(4):609-617.

Wilde DC, Castro PD, Bera K, Lai S, Madabhushi A, Corredor G, Koyuncu C, Lewis JS Jr, Lu C, Frederick MJ, Frederick AM, Haugen AE, Zevallos JP, Sturgis EM, Shi J, Huang AT, Hernandez DJ, Skinner HD, Kemnade JO, Yu W, Sikora AG, Sandulache VC. Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration. Mod Pathol. 2022 Aug;35(8):1045-1054. 

Koyuncu CF, Lu C, Bera K, Zhang Z, Xu J, Toro P, Corredor G, Chute D, Fu P, Thorstad WL, Faraji F, Bishop JA, Mehrad M, Castro PD, Sikora AG, Thompson LD, Chernock RD, Lang Kuhs KA, Luo J, Sandulache V, Adelstein DJ, Koyfman S, Lewis JS Jr, Madabhushi A. Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma. J Clin Invest. 2021 Apr 15;131(8):e145488.

Clinicians at Baylor College of Medicine provide cancer care to a diverse patient population through our affiliated hospitals which include the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) and Ben Taub General Hospital (BTGH). Our researchers have embraced this diverse patient population over the last decade, in order to:

1. Understand social, epidemiologic and biological drivers of disparate oncologic outcomes
2. Develop treatment algorithms which can deliver state of the science oncologic treatments with high NCCN compliance across these patient population

Our clinical studies have demonstrated equivalent oncologic outcomes are possible when health delivery systems provide consistent delivery of treatment to all patients that present with head and neck cancer in a manner compliant with NCCN-guidelines. Active research efforts are directed toward determining whether environmental exposures, or intrinsic tumor characteristics interact with head and neck cancer treatment regimens to potential drive disparate oncologic outcomes even in the setting of equitable cancer care delivery.

Recent Publications:

Fullmer TM, Shi J, Skinner HD, Hernandez DJ, Huang AT, Mai W, Parke RB, Donovan DT, Sandulache VC. Early glottic cancer in a veteran population: Impact of race on management and outcomes. Laryngoscope. 2020 Jul;130(7):1733-1739. doi: 10.1002/lary.28262. Epub 2019 Aug 28. PMID: 31461171.
Fullmer T, Wilde DC, Shi JW, Wagner T, Skinner H, Eicher SA, Sandulache VC, Hernandez DJ. Demographic and Tumor Characteristic Impact on Laryngeal Cancer Outcomes in a Minority Underserved Patient Population. Otolaryngol Head Neck Surg. 2020 Jun;162(6):888-896. doi: 10.1177/0194599820907064. Epub 2020 Feb 25. PMID: 32093532.

Florez MA, Kemnade JO, Chen N, Du W, Sabichi AL, Wang DY, Huang Q, Miller-Chism CN, Jotwani A, Chen AC, Hernandez D, Sandulache VC. Persistent ethnicity-associated disparity in anti-tumor effectiveness of immune checkpoint inhibitors despite equal access. Cancer Res Commun. 2022 Jul 26;2022:10.1158/2767-9764.CRC-21-0143. doi: 10.1158/2767-9764.CRC-21-0143. PMID: 35966167; PMCID: PMC9367161.

Koyuncu CF, Nag R, Lu C, Corredor G, Viswanathan VS, Sandulache VC, Fu P, Yang K, Pan Q, Zhang Z, Xu J, Chute DJ, Thorstad WL, Faraji F, Bishop JA, Mehrad M, Castro PD, Sikora AG, Thompson LDR, Chernock RD, Lang Kuhs KA, Wasman JK, Luo JR, Adelstein DJ, Koyfman SA, Lewis JS Jr, Madabhushi A. Image analysis reveals differences in tumor multinucleations in Black and White patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cancer. 2022 Nov 1;128(21):3831-3842. 

Piyarathna DWB, Balasubramanian A, Arnold JM, Lloyd SM, Karanam B, Castro P, Ittmann MM, Putluri N, Navone N, Jones JA, Yu W, Sandulache VC, Sikora AG, Michailidis G, Sreekumar A. ERR1 and PGC1α associated mitochondrial alterations correlate with pan-cancer disparity in African Americans. J Clin Invest. 2019 Mar 28;129(6):2351-2356. 

Liu Y, Kramer JR, Sandulache VC, Yu R, Li G, Chen L, Yusuf ZI, Shi Y, Pyarajan S, Tsavachidis S, Jiao L, Mierzwa ML, Chiao E, Mowery YM, Shuman A, Shete S, Sikora AG, White DL. Immunogenetic Determinants of Susceptibility to Head and Neck Cancer in the Million Veteran Program Cohort. Cancer Res. 2022 Nov 15;CAN-22-1641.

Dr. Julina Ongkasuwan, who has a joint appointment with Texas Children’s Hospital, is pioneering the use of laryngeal ultrasound (LUS) in both the pediatric and adult populations. With grant funding from the Thrasher Research Fund, she established the imaging criteria and demonstrated vocal fold immobility in neonates after congenital heart surgery. This promises to become a reliable diagnostic tool beyond flexible nasopharyngolaryngoscopy in high risk populations.

Receiving grant funding from the Texas Children’s Hospital Department of Surgery, Dr. Ongkasuwan is also exploring the use of LUS for the identification of vocal fold nodules. While the diagnosis is typically via laryngeal stroboscopy, LUS may be used to further characterize vocal fold lesions.

Investigators at Baylor College of Medicine and Texas Children’s Hospital utilize a variety of clinical tools to optimize the early diagnosis of vocal fold motion impairment and glottic incompetence in the setting of trauma, iatrogenic injury and prolonged intubation. These efforts are paralleled by active clinical research focused on the restoration of vocal fold mobility through laryngeal re-innervation techniques.

Recent Publications: 

Kobayashi K, You P, Devore D, Hollas S, Geraghty JR, Ongkasuwan J. Endoscopic posterior rotation flap for posterior glottic insufficiency. Laryngoscope. 2022 Jul;132(7):1452-1454.

Narawane A, Rappazzo C, Hawney J, Clason H, Roddy DJ, Ongkasuwan J. Vocal Fold Movement and Silent Aspiration After Congenital Heart Surgery. Laryngoscope. 2022 Mar;132(3):701-705. 

Alexander NL, Tran B, Zhu H, Ongkasuwan J. Learning to Interpret Pediatric Vocal Fold Mobility – A Laryngeal Ultrasound Training Module. Laryngoscope. 2021 Nov;131(11):2545-2549. 

Ongkasuwan J, Espinosa M, Procter T, Bassett E, Devore D, Hollas S, Schwabe A. Predictors of voice outcome in pediatric non-selective laryngeal reinnervation. Laryngoscope. 2020 Jun;130(6):1525-1531.   

In order to safely match treatment intensity to oropharyngeal cancer (OPC) biology, biomarkers of treatment response must be developed and tailored to individual OPC patients. Both aggressive and biologically favorable tumors, respectively, manifest their own unique phenotypic alterations that can be appreciated using standard clinical, pathologic and radiologic datasets. Computationally derived biomarkers derived from both radiology and pathology images can enable prediction of disease progression and response to therapy for all subgroups of patients and stratify patient risk in a way that is superior to clinical parameters alone (e.g., T-, N-stage; detailed Preliminary Data is provided in the following sections). Our multi-disciplinary, multi-institutional team seeks to develop an AI based Risk Stratification for Oropharyngeal Carcinomas (AIROC) platform that will utilize radiomic and pathomic imaging biomarkers in addition to clinical factors to predict OPC response to treatment, tailored to individual patient tumors. This work, led by Dr. Vlad Sandulache (BCM) and Dr. Anant Madabhushi (Emory University) is supported by the Veterans Affairs Office of Research and Development and represents the largest collaborative project within the Veterans Health Administration focused on head and neck cancer within the last 2 decades.

Recent publications:

Sandulache VC, Kirby RP, Lai SY. Moving from conventional to adaptive risk stratification for oropharyngeal cancer. Front Oncol. 2024 Mar 14:14:1287010. doi: 10.3389/fonc.2024.1287010. eCollection 2024.

Koyuncu CF, Frederick MJ, Thompson LDR, Corredor G, Khalighi S, Zhang Z, Song B, Lu C, Nag R, Sankar Viswanathan V, Gilkey M, Yang K, Koyfman SA, Chute DJ, Castro P, Lewis JS Jr, Madabhushi A, Sandulache VC. Machine learning driven index of tumor multinucleation correlates with survival and suppressed anti-tumor immunity in head and neck squamous cell carcinoma patients. Oral Oncol. 2023 Aug:143:106459.

Wilde DC, Castro PD, Bera K, Lai S, Madabhushi A, Corredor G, Koyuncu C, Lewis JS Jr, Lu C, Frederick MJ, Frederick AM, Haugen AE, Zevallos JP, Sturgis EM, Shi J, Huang AT, Hernandez DJ, Skinner HD, Kemnade JO, Yu W, Sikora AG, Sandulache VC. Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration. Mod Pathol. 2022 Aug;35(8):1045-1054.

Corredor G, Toro P, Koyuncu C, Lu C, Buzzy C, Bera K, Fu P, Mehrad M, Ely KA, Mokhtari M, Yang K, Chute D, Adelstein DJ, Thompson LDR, Bishop JA, Faraji F, Thorstad W, Castro P, Sandulache V, Koyfman SA, Lewis JS, Madabhushi A. An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer. J Natl Cancer Inst. 2022 Apr 11;114(4):609-617.

Koyuncu CF, Lu C, Bera K, Zhang Z, Xu J, Toro P, Corredor G, Chute D, Fu P, Thorstad WL, Faraji F, Bishop JA, Mehrad M, Castro PD, Sikora AG, Thompson LD, Chernock RD, Lang Kuhs KA, Luo J, Sandulache V, Adelstein DJ, Koyfman S, Lewis JS Jr, Madabhushi A. Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma. J Clin Invest. 2021 Apr 15;131(8):e145488.