About

Devraj Basu, M.D., Ph.D., F.A.C.S., is an Associate Professor of Otorhinolaryngology: Head and Neck Surgery at the Hospital of the University of Pennsylvania. He is a full member of the Abramson Cancer Center Therapeutics Program and leads the Translational Center of Excellence for HPV+ Head and Neck Cancer at the Abramson Cancer Center, University of Pennsylvania. His research focuses on improving the ability to cure the most aggressive head and neck cancers while reducing treatment toxicity for those that are readily curable by existing therapies. His laboratory investigates how multiple subpopulations of malignant cells within tumors cooperate to resist therapy through both tumor cell autonomous mechanisms and crosstalk with the stromal microenvironment. His work involves analyzing heterogeneity and phenotypic plasticity within cancer cell lines, patient-derived xenografts, and primary human cancer samples based on molecular and functional criteria. He aims to define the epigenetic plasticity that promotes tumor cell homeostasis and malignant potential despite standard treatments, integrating known drug resistance mechanisms into a framework where oncogenic signaling pathways are regulated by flux between distinct cell states. His research demonstrates the heterogeneity and plasticity of oncogenic signaling within tumors and exploits intra-tumor diversity to improve targeted therapy efficacy. Clinically, Dr. Basu manages complex head and neck cancer cases as an oncologic and reconstructive surgeon at the Hospital of the University of Pennsylvania. He employs open, endoscopic, robotic, and laser procedures to treat benign and malignant disorders of the mouth, throat, larynx, nose, sinuses, salivary glands, parapharyngeal space, and skin, and is highly experienced in surgical management of thyroid and parathyroid diseases. His clinical expertise includes managing HPV-related cancers, squamous cell carcinomas, salivary and nasal cancers, skin cancers, thyroid cancers, and benign tumors of the head and neck, among others. His work integrates cutting-edge molecular research with surgical care to optimize patient outcomes and advance cancer therapy.

Research topics

• Medicine
• Internal medicine
• Oncology
• Surgery
• Pathology
• Biology
• Cancer research

Selected publications

• Cigarette Smoke Exposure Attenuates <scp>T2R</scp> ‐Mediated Apoptosis in Head and Neck Squamous Cell Carcinoma

  Head & Neck · 2026-04-25

  articleOpen access

  BACKGROUND: Tobacco use is associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). Bitter taste receptor (T2R) activation induces apoptosis via calcium-dependent signaling, and higher T2R expression correlates with increased survival in HNSCC. However, the effects of cigarette smoke on T2R signaling remain unclear. METHODS: HNSCC cell lines were treated with cigarette smoke condensate (CSC). T2R expression was measured by qPCR, and function evaluated by calcium imaging, viability, and apoptosis assays following stimulation with denatonium benzoate and flufenamic acid. T2R expression was also assessed in patient-derived tumor tissue and The Cancer Genome Atlas (TCGA). RESULTS: CSC reduced T2R expression, impaired calcium signaling, and diminished T2R-mediated apoptosis, particularly in SCC47 cells. Lower expression was observed in CSC-exposed patient-derived tumor tissue and TCGA tumors from smokers versus nonsmokers. CONCLUSIONS: Cigarette smoke disrupts T2R signaling and reduces apoptosis in HNSCC, suggesting a mechanism by which ongoing tobacco use may alter tumor biology and treatment response.

  PublisherDOI

• E2 displacement of CIP2A from TOPBP1 activates the DNA damage response during papillomavirus life cycles

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-15 · 3 citations

  preprintOpen access

  The papillomavirus life cycle is intricately linked to epithelial differentiation, and the virus manipulates the differentiation process to facilitate viral production. One such manipulation is activation of the DNA damage response (DDR) which promotes viral replication via homologous recombination. This report demonstrates that the papillomavirus transcription/replication/segregation factor E2 activates the DNA damage response (DDR). During differentiation, E2 displacement of CIP2A from TOPBP1 causes CIP2A to bind and inhibit PP2A resulting in DDR activation via ATM phosphorylation. The DDR promotes inhibitory interaction of DBC1 with the class III deacetylase SIRT1, which further boosts the DDR via increased acetylation and stability of viral and host proteins. E2 forms a complex with TOPBP1 and ATM, while preventing ATR activation by blocking TOPBP1-ATR interaction. This "ATM up ATR down" phenotype promotes viral replication via ATM promotion of homologous recombination, and cell proliferation via inhibition of ATR. We demonstrate this mechanism of DDR activation in multiple systems: keratinocytes expressing only E2, in foreskin keratinocytes immortalized by HPV16, in HPV16 positive keratinocytes derived from a cervical lesion, in pre-neoplastic lesions induced by mouse papillomavirus MmuPV1, in head and neck cancer cell lines that retain E2 expression, and in HPV16 positive oropharyngeal patient derived xenografts that retain E2 expression. ATM inhibition preferentially killed cells expressing E2, presenting a novel strategy for treating HPV early preneoplasia and a large subset of HPV+ oropharyngeal cancers retaining E2 expression and episomal genomes.

  PublisherOA PDFDOI

• Analysis of AI foundation model features decodes the histopathologic landscape of HPV-positive head and neck squamous cell carcinomas

  Oral Oncology · 2025-03-03 · 9 citations

  article
  PublisherDOI

• Abstract 2471: Interpretable HPV detection in head and neck cancer using foundation models and synthetic digital pathology

  Cancer Research · 2025-04-21

  article

  Abstract Introduction: Detecting human papillomavirus (HPV) status is crucial for treating Head and Neck Squamous Cell Carcinomas (HNSCCs). While p16 immunohistochemistry is the current standard for HPV detection, its moderate sensitivity and complex implementation limit its global utility. The ability to diagnose HPV status in HNSCC has become increasingly critical worldwide, as rising HPV-positive HNSCC rates observed in high-income countries may signal a global trend, and HPV status remains essential for treatment selection. Although hematoxylin and eosin (H&amp;E) stained slides are clinically ubiquitous, artificial intelligence (AI) methods applied to these images have not matched molecular assays’ performance nor provided needed clinical interpretability. Recent advances in vision transformer-based foundation models for computational pathology offer a promising approach to address this unmet need. Methods: We analyzed H&amp;E images from 981 HNSCC patients across four datasets: TCGA (n=HPV+ 33/total 401), CPTAC (n=1/109), UCH (n=159/364), and PENN (n=106/106). Fifty percent of the patients were used for validation. Using UNI, a foundation self-supervised learning (SSL) model, we extracted feature vectors from 10x effective magnification tile images across each whole slide. We identified an HPV feature axis using recursive support vector machine and principal component analysis to isolate SSL features that differentiated HPV tumors, then interpreted the relevant histologic features using HistoXGAN to generate synthetic histology images. This approach enabled the isolation of histologic features specific to HPV+ tumors, whereas real histology images contain multiple sources of variation. An expert pathologist validated the biological relevance of the identified HPV-axis features. We developed a predictive model for HPV status by varying the percentages of tiles within each slide required to exceed a binary threshold on the HPV-axis. This model was robust across threshold choices. Results: Our method identified an HPV-axis that robust HPV detection performance (sensitivity 0.83, specificity 0.88) across all datasets (balanced accuracy - TCGA 0.77, CPTAC 0.98, UCH 0.78, PENN 1.00). Using synthetic histology images and pathologist validation, we identified key, morphological features aligning with established HPV-associated histology, including nuclei size, color, and cell borders. Together with our Grundium slide scanning pipeline the time-to-prediction for a slide is less than 3 minutes. Conclusions: Foundation models and synthetic digital pathology enabled HPV detection from histology with accuracy comparable to current diagnostic standards, while providing pathologist-interpretable predictions. This accessible, rapid, and explainable method holds promise for expanding testing of HPV and potentially other molecular features in resource-limited settings. Citation Format: Hanna M. Hieromnimon, Anna Trzcinska, Frank Wen, Frederick M. Howard, James M. Dolezal, Emma Dyer, Sara Kochanny, Jefree Schulte, Cindy Wang, Heather Chen, Jeffrey Chin, Elizabeth Blair, Nishant Agrawal, Ari Rosenberg, Everett Vokes, 1 Rohan Katipally, Aditya Juloori, Evgeny Izumchenko, Mark W. Lingen, Nicole Cipriani, Jalal B. Jalaly, Devraj Basu, Samantha J. Riesenfeld, Alexander T. Pearson. Interpretable HPV detection in head and neck cancer using foundation models and synthetic digital pathology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2471.

  PublisherDOI

• Corrigendum to “Analysis of AI foundation model features decodes the histopathologic landscape of HPV-positive head and neck squamous cell carcinomas”. [Oral Oncol. 163 (2025) 107207]

  Oral Oncology · 2025-07-28

  erratum
  PublisherDOI

• Prognostic Implications of Detectable Postoperative Tumor Tissue-Modified HPV DNA in Patients with p16+ Oropharyngeal Squamous Cell Carcinoma Undergoing De-Intensified Adjuvant Radiation

  International Journal of Radiation Oncology*Biology*Physics · 2025-09-01

  article
  PublisherDOI

• Outcomes of <scp>HPV</scp> + Oropharyngeal Carcinoma of Unknown Primary Following Transoral Robotic Surgery

  The Laryngoscope · 2025-08-13 · 2 citations

  articleOpen access

  OBJECTIVES: Treatment of patients with head and neck squamous cell carcinoma of unknown primary (CUP) is challenging. Given the relative rarity of this condition and the recent use of primary transoral robotic surgery (TORS) in modern diagnostic and treatment algorithms, long-term oncologic outcomes are unclear. The objectives were to evaluate oncologic outcomes of patients treated with TORS for management of CUP. METHODS: This retrospective case series was conducted at a tertiary care academic medical center from 2010 to 2021. All patients with HPV-mediated CUP who underwent TORS-assisted endoscopy were included. CUP was defined as biopsy-proven squamous cell carcinoma in a cervical lymph node with uncertain primary location following standard-of-care clinical and radiologic assessment. Primary outcomes were recurrence-free survival and overall survival. Secondary outcomes included usage of radiation and chemotherapy. RESULTS: In total, 157 patients were included in the study. Median follow-up time was 62 months. Primary tumor was identified in 88% of patients. Surgery alone was performed in 21%, although adjuvant therapy was recommended but declined in 13%. Adjuvant radiation was completed in 46% and adjuvant chemoradiation in 33%. Two-thirds of patients avoided chemoradiation. Overall survival was 94% and recurrence-free survival was 92% at 5 years. CONCLUSION: In the largest reported experience to date of TORS-assisted management of CUP, we demonstrate that this approach facilitates a high rate of identification of occult mucosal malignancies and can eliminate the need for chemotherapy and potentially radiation therapy in select patients without compromising excellent oncologic and functional outcomes.

  PublisherOA PDFDOI

• Preoperative Circulating Tumor HPV DNA and Oropharyngeal Squamous Cell Disease

  JAMA Otolaryngology–Head & Neck Surgery · 2024-04-04 · 12 citations

  articleOpen access

  Importance: The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown. Objective: To determine if preoperative circulating tumor HPV DNA (ctHPVDNA) is associated with disease burden in patients with HPV+ OPSCC who have undergone transoral robotic surgery (TORS). Design, Setting, and Participants: This cross-sectional study comprised patients with HPV+ OPSCC who underwent primary TORS between September 2021 and April 2023 at one tertiary academic institution. Patients with treatment-naive HPV+ OPSCC (p16-positive) and preoperative ctHPVDNA levels were included, and those who underwent neck mass excision before ctHPVDNA collection were excluded. Main Outcomes and Measures: The main outcome was the association of increasing preoperative ctHPVDNA levels with tumor size and lymph node involvement in surgical pathology. The secondary outcome was the association between preoperative ctHPVDNA levels and adverse pathology, which included lymphovascular invasion, perineural invasion, or extranodal extension. Results: A total of 70 patients were included in the study (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ctHPVDNA levels ranged from 0 fragments/milliliter of plasma (frag/mL) to 49 452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 patients (83%) had positive results for ctHPVDNA, 1 (1.4%) had indeterminate results, and 11 (15.6%) had negative results. The sensitivity of detectable ctHPVDNA for identifying patients with pathology-confirmed HPV+ OPSCC was 84%. Twenty-seven patients (39%) had pathologic tumor (pT) staging of pT0 or pT1, 34 (49%) had pT2 staging, and 9 patients (13%) had pT3 or pT4 staging. No clinically meaningful difference between detectable and undetectable preoperative ctHPVDNA cohorts was found for tumor size or adverse pathology. Although the median preoperative ctHPVDNA appeared to be higher in pT2 through pT4 stages and pN1 or pN2 stages, effect sizes were small (pT stage: η2, 0.002 [95% CI, -1.188 to 0.827]; pN stage: η2, 0.043 [95% CI, -0.188 to 2.600]). Median preoperative log(TTMV-HPV DNA) was higher in active smokers (8.79 [95% CI, 3.55-5.76]), compared with never smokers (5.92 [95% CI, -0.97 to 1.81]) and former smokers (4.99 [95% CI, 0.92-6.23]). Regression analysis did not show an association between tumor dimension or metastatic lymph node deposit size and preoperative log(TTMV-HPV DNA). After univariate analysis, no association was found between higher log(TTMV-HPV DNA) levels and adverse pathology. Conclusions and Relevance: In this cross-sectional study, preoperative ctHPVDNA levels were not associated with disease burden in patients with HPV+ OPSCC who underwent TORS.

  PublisherOA PDFDOI

• HPV16 genome structure analysis in oropharyngeal cancer PDXs identifies tumors with integrated and episomal genomes

  Tumour Virus Research · 2024-06-25 · 16 citations

  articleOpen accessCorresponding

  HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related cancer in the developed world. HPV16 is in ∼90 % of HPV + OPCs, with episomal genomes in the majority of cases. Most existing HPV16+ cancer cell lines derive from outside the oropharynx and harbor integrated HPV genomes. Thus, there is need for OPC preclinical models to evaluate standard and experimental therapeutics in the presence of episomal HPV16 oncogenic drivers. Here we characterize HPV genome structures in eight HPV16+ OPC patient-derived xenografts (PDXs), and evaluate their responses to standard chemotherapy. HPV genome state was investigated by combining Southern blot, T5 exonuclease assay, whole genome sequencing, and RNAseq data. This analysis revealed complexity and variation in integrated vs. episomal HPV forms across PDXs and demonstrated that four PDXs predominantly contain episomal HPV16. Episomal status did not ensure favorable in vivo responses to cisplatin therapy, despite the more favorable prognosis previously attributed to episomal HPV + tumors; this could be due to the small number present in the dataset. Our analysis establishes PDX models as test platforms for novel therapies designed to target maintenance of the episomal forms of HPV16 that commonly appear in OPC.

  PublisherDOI

• Radiomic features associated with recurrence in a case:control cohort of surgically treated HPV+ OPSCC

  International Journal of Radiation Oncology*Biology*Physics · 2024-03-14

  article
  PublisherDOI

Recent grants

• Targeting mesenchymal-like cells in oral cancer to overcome cetuximab resistance

  NIH · $669k · 2012–2017

• NIH Grant R21DE024396

  NIH · $453k · 2017

• JARID1B-mediated epigenetic regulation of oncogenic signals in oral cancer

  NIH · $362k · 2017–2018

• JARID1B-mediated epigenetic regulation of oncogenic signals in oral cancer

  NIH · $1.5M · 2018–2023

Frequent coauthors

• Meenhard Herlyn

  82 shared

• Phyllis A. Gimotty

  79 shared

• Anil K. Rustgi

  Columbia University Irving Medical Center

  74 shared

• Hiroshi Nakagawa

  58 shared

• Gregory S. Weinstein

  University of Pennsylvania

  52 shared

• J. Alan Diehl

  52 shared

• Andres J. Klein‐Szanto

  48 shared

• Iain M. Morgan

  Virginia Commonwealth University

  47 shared