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Advances in the Management of Oropharyngeal Cancer: Navigating the HPV-Associated Landscape

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 5337

Special Issue Editor


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Guest Editor
1. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
2. Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Interests: oropharyngeal; squamous; cell; carcinoma; management; surgery; surgical

Special Issue Information

Dear Colleagues,

We are pleased to introduce this Special Issue dedicated to the comprehensive exploration of the latest advancements in the management of oropharyngeal cancer, a complex and increasingly prevalent malignancy that poses significant challenges to both patients and healthcare providers. Over recent years, the landscape of oropharyngeal cancer has changed dramatically, marked by a notable increase in cases associated with human papillomavirus (HPV) infection. This issue will provide an in-depth examination of various facets of oropharyngeal cancer, encompassing topics ranging from screening and epidemiology to clinical trials, surgical interventions, radiation therapy, surveillance including novel liquid biopsy methods, chemotherapy, complications associated with treatment, reconstructive options, and the management of recurrent and metastatic disease.

Our aim is to offer a multidisciplinary perspective of oropharyngeal cancer management, incorporating the insights of leading experts in the field to present the most up-to-date research findings, clinical guidelines and emerging therapies. We will delve into the evolving landscape of screening and early detection strategies, providing critical insights into improving outcomes through timely diagnosis. Additionally, we will explore the epidemiological trends and risk factors associated with oropharyngeal cancer, with a particular emphasis on the increasing prevalence of HPV-related cases and its impact on disease management and prognosis. Furthermore, this Special Issue will encompass the latest developments in surgical techniques, radiation therapy modalities, chemotherapy regimens and their combinations to optimize treatment outcomes while minimizing the side effects. We will also delve into the challenges posed by complications arising from treatment and the various reconstructive options available to restore function and aesthetics in patients' post-treatment lives. Finally, we will address the complex issues surrounding recurrent and metastatic oropharyngeal cancer, discussing cutting-edge approaches to management and emerging therapeutic options, including those tailored to HPV-positive cases. We believe this compilation of articles will serve as a valuable resource for healthcare professionals and researchers committed to advancing the care and understanding of oropharyngeal cancer in the context of its changing landscape, marked by the increasing incidence of HPV-associated cases.

Dr. Jon Mallen-St Clair
Guest Editor

Manuscript Submission Information

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Keywords

  • oropharyngeal cancer
  • human papillomavirus
  • clinical trials
  • transoral robotic surgery
  • epidemiology
  • HPV-related oropharyngeal cancer

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Published Papers (3 papers)

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Research

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15 pages, 2442 KB  
Article
Indisulam Shows an Anti-Cancer Effect on HPV+ and HPV− Head and Neck Cancer
by Tara M. Hosseini, Sophie S. Jang, Joseph Bendik and Theresa Guo
Cancers 2025, 17(7), 1072; https://doi.org/10.3390/cancers17071072 - 22 Mar 2025
Cited by 1 | Viewed by 2093
Abstract
Background/Objectives: HPV+ head and neck squamous cell carcinoma has been shown to have a unique genomic background, requiring researchers to study it as its own distinct type of cancer. HPV+ tumors have been shown to exhibit fewer genetic mutations in cancer drivers [...] Read more.
Background/Objectives: HPV+ head and neck squamous cell carcinoma has been shown to have a unique genomic background, requiring researchers to study it as its own distinct type of cancer. HPV+ tumors have been shown to exhibit fewer genetic mutations in cancer drivers as opposed to their HPV− counterparts. In this paper, we explored how targeting post-transcriptional changes, specifically alternative splicing events, could serve as a potential mechanism to treat HPV+ cancer. Methods: Using indisulam, a drug that targets alternative splicing through the degradation of RBM39, we treated various HPV+ and HPV− cell lines and assessed tumor cell viability. We also tested indisulam in vivo to evaluate its effect on tumor volume. Additionally, we analyzed gene expression differences between indisulam-treated subjects and their non-treated counterparts. Results: Indisulam treatment led to a reduction in tumor cell viability in both HPV+ and HPV− cell lines. In vivo experiments showed a reduction in tumor volume following indisulam treatment. Gene expression analysis revealed that indisulam induces consistent differential gene expression changes and highly enriches interferon pathways in treated HPV+ cell lines. Conclusions: These findings suggest that targeting alternative splicing via indisulam may be a promising therapeutic approach for HPV+ cancers. Further research is required to establish indisulam as a viable anti-cancer treatment in clinical settings. Full article
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Review

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42 pages, 424 KB  
Review
Quantitative Imaging Advances in HPV-Positive Oropharyngeal Carcinoma
by Dermot Farrell, Houda Bahig, Richard Khor, Luiz P. Kowalski, Remco de Bree, Avraham Eisbruch, Heleen Bollen, Fernando Lopez, M. P. Sreeram, Orlando Guntinas-Lichius, Juan P. Rodrigo, Nabil F. Saba, Karthik N. Rao, Sandra Nuyts, Anna Luíza Damaceno Araújo, Alfio Ferlito and Sweet Ping Ng
Cancers 2026, 18(2), 303; https://doi.org/10.3390/cancers18020303 - 19 Jan 2026
Viewed by 880
Abstract
HPV-positive OPSCC shows a favourable prognosis, prompting evaluation of de-escalated and adaptive strategies. Quantitative imaging may provide scalable biomarkers to individualise care. Quantitative imaging can support baseline risk stratification, early on-treatment decision-making, and posttreatment surveillance in HPV-positive OPSCC. Real-world translation requires standardised reporting, [...] Read more.
HPV-positive OPSCC shows a favourable prognosis, prompting evaluation of de-escalated and adaptive strategies. Quantitative imaging may provide scalable biomarkers to individualise care. Quantitative imaging can support baseline risk stratification, early on-treatment decision-making, and posttreatment surveillance in HPV-positive OPSCC. Real-world translation requires standardised reporting, calibration/harmonisation across centres, rigorous model validation, and workflow integration with radiotherapy planning. Quantitative MRI, CT, and PET, augmented by radiomics and AI, show convergent promise as non-invasive biomarkers to enable safe individualisation of therapy in HPV-positive OPSCC, contingent on methodological rigour and prospective, externally validated studies. Despite this promise, clinical translation faces substantial barriers, including limited external validation, heterogeneous methodologies, and the need for standardised, prospectively validated pipelines. Full article
12 pages, 2110 KB  
Review
Detection of Human Papillomavirus (HPV) in HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Review of Diagnostic Approach and Its Importance for the Head and Neck Oncologist
by Amanda J. Bastien, Daniel Manzoor, Evan S. Walgama, Kevin S. Scher, Julie K. Jang, Justin Moyers, Zachary S. Zumsteg, Allen S. Ho and Jon Mallen-St. Clair
Cancers 2026, 18(1), 56; https://doi.org/10.3390/cancers18010056 - 24 Dec 2025
Cited by 2 | Viewed by 1540
Abstract
Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status [...] Read more.
Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status in OPSCC. It covers both traditional methods—such as p16 immunohistochemistry, HPV in situ hybridization, and DNA polymerase chain reaction (PCR)—and newer, evolving strategies including circulating HPV tumor DNA analysis and oral HPV DNA/mRNA PCR testing. Discussion: There are currently several histopathologic techniques for the diagnosis of HPV-associated OPSCC. This complexity of care has led to guidelines from numerous authorities (NCCN, ASCO, CAP), which this paper discusses and summarizes for head and neck oncology specialists. Conclusion: The ability to detect HPV in HPV-associated OPSCC is imperative for diagnosis, prognostication, staging, and management of the disease. Advances including liquid biopsy (TTMV-HPV DNA) may be utilized as an adjunct to diagnosis, treatment, and cancer surveillance in the future. Full article
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