Human Papillomavirus-positive Oropharyngeal Cancer - Market Insight, Epidemiology, and Market Forecast - 2034

Key Highlights:

• With declining rates of head and neck cancers related to alcohol and tobacco, HPV has become the principal etiologic factor in OPSCC, redefining prognostic outlooks and informing the development of tailored therapeutic approaches.
• Patients with HPV-positive oropharyngeal tumors exhibit significantly better prognosis and higher curability compared to HPV-negative counterparts receiving identical treatment.
• American and European guidelines for managing oropharyngeal squamous cell carcinoma (OPSCC) patients do not vary based on the HPV status of the tumor.
• OPSCC is frequently diagnosed at an advanced stage due to minimal early symptoms, underscoring the critical need for identifying and validating diagnostic biomarkers to enable earlier, more effective detection.
• Intensity-modulated radiation therapy (IMRT) remains the standard first-line treatment for early-stage OPSCC, though transoral robotic surgery (TORS) offers a viable alternative in select cases. HPV-positive patients demonstrate superior overall survival following primary IMRT but often experience longer-lasting functional impairments, underscoring the importance of weighing oncologic benefit against long-term quality-of-life outcomes.
• Immunotherapy may be more effective in HPV-positive patients, but its molecular mechanism is not yet fully understood. However, HPV status does not influence immunotherapy indications in recurrent or metastatic OPSCC.
• Advanced-stage oropharyngeal cancers are optimally managed with radiotherapy, often in combination with chemotherapy, while p16 positivity serves as a robust prognostic biomarker, correlating with significantly improved clinical outcomes.
• Open transpharyngeal and transmandibular approaches are best reserved for salvage settings. In carefully selected patients, transoral salvage surgery may offer superior functional and oncologic outcomes, supporting its strategic role in recurrence management.
• KEYTRUDA monotherapy is the preferred first-line treatment for recurrent or metastatic HNSCC with high PD-L1 expression. However, only about 20% of patients respond, and there is no significant difference based on HPV status. Currently, no treatments are specifically approved for HPV16+ cancers.
• Due to limited survival benefits, added costs, and potential functional impairments, definitive CRT should be the primary treatment for most HPV-positive locally advanced OPSCC patients, with surgery as a last resort.
• The pipeline for oropharyngeal cancer is rising, with Merck Sharp & Dohme (KEYTRUDA), Bristol Myers Squibb (OPDIVO), PDS Biotechnology (Versamune HPV/PDS0101), Inovio Pharmaceuticals and MedImmune (INO-3112/MEDI0457), Cue Biopharma (CUE-101), and others in clinical development.

DelveInsight's "Human Papillomavirus-positive (HPV+) Oropharyngeal Cancer- Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of oropharyngeal cancer, historical and forecasted epidemiology as well as HPV+ oropharyngeal cancer market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The HPV+ oropharyngeal cancer market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM HPV+ oropharyngeal cancer market size from 2020 to 2034. The report also covers current HPV+ oropharyngeal cancer treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered:

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

HPV+ Oropharyngeal Cancer: Understanding and Treatment Algorithm

Oropharyngeal Cancer Overview

Oropharyngeal cancer is a subtype of head and neck cancer that arises in the oropharynx, the middle part of the pharynx, located behind the oral cavity. It commonly affects areas such as the back one-third of the tongue, soft palate, tonsils, and the side and back walls of the throat. The majority of oropharyngeal cancers are squamous cell carcinomas, which originate in the squamous cells, thin, flat cells that line the surface of many organs, including the oropharynx. Less commonly, lymphoma may develop in this region, particularly in the base of the tongue or tonsils, both of which contain lymphatic tissue. Major risk factors for oropharyngeal cancer include tobacco use, heavy alcohol consumption, and infection with HPV, particularly HPV type 16, which is strongly associated with HPV-positive oropharyngeal cancer.

HPV+ Oropharyngeal Cancer Diagnosis

The diagnosis of HPV-positive oropharyngeal cancer relies on a combination of clinical evaluation, imaging, tissue sampling, and HPV testing. Patients often present with subtle symptoms such as a persistent sore throat, dysphagia, or a neck mass from nodal metastasis, prompting a thorough head and neck examination, including flexible endoscopy. Imaging with contrast-enhanced CT or MRI is used to define local tumor extent and nodal disease, while PET-CT can aid in staging and detecting distant metastases. A definitive diagnosis requires tissue confirmation, usually through biopsy of the primary lesion or fine-needle aspiration of an involved cervical node; when the primary tumor is not apparent, panendoscopy with directed biopsies or tonsillectomy may be necessary. Determining HPV status is critical for prognosis and treatment planning, with p16 immunohistochemistry serving as the recommended surrogate marker, and confirmatory HPV DNA or RNA testing reserved for select cases. Staging is then performed according to the AJCC 8th edition, which provides a separate classification system for HPV-mediated (p16-positive) oropharyngeal cancers.

HPV+ Oropharyngeal Cancer Treatment

HPV-positive OPSCC detected at early stages is generally managed with single-modality therapy, either surgery with selective neck dissection or definitive radiation therapy. TORS has emerged as a minimally invasive surgical option, though adjuvant therapy is required in cases with adverse pathological features such as positive margins or extranodal extension. Most OPSCC cases, however, are diagnosed at advanced stages with nodal involvement, necessitating multimodality treatment (typically CRT or surgery plus adjuvant CRT), which is effective but associated with long-term toxicities. Given the favorable prognosis of HPV-positive disease, there is significant interest in de-intensification strategies to reduce treatment-related morbidity, although randomized Phase III data are still needed before such approaches can be adopted as standard practice. Earlier detection of precancerous lesions may allow for safe use of monotherapy with fewer complications, while ongoing research into the progression from HPV infection to malignancy may support future development of preventive strategies.

HPV+ Oropharyngeal Cancer Epidemiology

The HPV+ oropharyngeal cancer epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total incident cases of head and neck cancer, total incident cases of HNSCC, total incident cases of OPSCC, OPSCC cases by HPV status, stage-specific cases of OPSCC, line-wise treated cases of OPSCC in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2020 to 2034.

• There were an estimated 170,000 incident cases of head and neck cancer across the 7MM in 2024, including nearly 150,000 cases of HNSCC.
• Among HNSCC, approximately 20,000 cases of OPSCC were reported in the US in 2024.
• Among stage-specific cases of HPV16+ OPSCC, regional stages (III-IVB) account for over 70%.
• In 2024, EU4 and the UK reported around 10,000 cases of OPSCC, with France contributing the highest number at approximately 4,000 cases, while Spain recorded the lowest, with fewer than 1,000 cases.

HPV+ Oropharyngeal Cancer Drug Chapters

The drug chapter segment of the oropharyngeal cancer report encloses a detailed analysis of HPV+ oropharyngeal cancer marketed drugs. It also deep dives into HPV+ oropharyngeal cancer pivotal clinical trial details, recent and expected market approvals, patent details, the latest news, and recent deals and collaborations.

Marketed Drugs

KEYTRUDA (pembrolizumab): Merck Sharp & Dohme

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody (mAb) that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells. As KEYTRUDA's US patent cliff nears in 2028, Merck faces tough choices and the need for new strategies.OPDIVO (nivolumab): Bristol Myers Squibb

OPDIVO is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's immune system to help restore anti-tumor immune response. By harnessing the body's immune system to fight cancer, OPDIVO has become an important treatment option across multiple cancers. While OPDIVO faces US patent expiry in 2028, the new SC formulation, OPDIVO QUANTIG, offers a chance to retain market edge and reach more patients.

Emerging Drugs

Versamune HPV (PDS0101): PDS Biotechnology

Versamune HPV (formerly PDS0101) is a novel investigational human papilloma virus (HPV)-targeted immunotherapy that stimulates a potent targeted T cell attack against HPV-positive cancers. Versamune HPV is given by a simple SC injection in combination with other immunotherapies and cancer treatments. Versamune HPV is currently being evaluated by us in a Phase III clinical trial in combination with pembrolizumab for treatment of OPSCC.

• In June 2025, PDS Biotechnology announced hosting of a virtual key opinion leader (KOL) event, to discuss the unmet need and current treatment landscape for recurrent/metastatic HPV16-positive HNSCC. The event reviews the changing landscape of HNSCC in context with Merck's KEYNOTE-689 (KN-689) study and the rapidly increasing incidences of HPV16-positive HNSCC in the US and Europe, also including, review of Versamune HPV, which is currently being evaluated in a Phase III clinical trial in combination with pembrolizumab as a first-line treatment for R/M HPV16+ HNSCC, as well as in Phase II clinical trials for the treatment of various types of HPV16-positive cancers.
• In June 2025, PDS Biotechnology announced publication of three Versamune HPV abstracts with clinical studies named: VERSATILE-002 and VERSATILE-003, presented at 2025 American Society of Clinical Oncology (ASCO) annual meeting.

INO-3112 (MEDI0457): Inovio Pharmaceuticals and MedImmune

INO-3112 is a DNA medicine candidate targeting HPV 16/18 combined with a DNA plasmid for IL-12 as an immune activator. INOVIO is investigating the potential benefit of the antigen-specific T cell generation and tumor infiltration abilities of INO-3112 in HPV-related cancers, especially when used in novel combinations.

• In January 2025, announced that it plans to gain alignment on planned Phase III trial design with European Union regulators. The trial is to be conducted in North America and Europe through a clinical collaboration and supply agreement signed in 2024 with Coherus BioSciences, evaluating the combination of INO-3112 and LOQTORZI (toripalimab-tpzi) in patients with locoregionally advanced, high-risk, HPV16/18-positive OPSCC.
• In January 2024, INOVIO announced a clinical collaboration and supply agreement with Coherus BioSciences to evaluate the combination of INO-3112 and LOQTORZI as a potential treatment for patients with locoregionally advanced, high-risk, HPV16/18 positive OPSCC. Combination therapy to be evaluated in a Phase III trial in patients with locoregionally advanced, high-risk, HPV16/18-positive head and neck cancer.

Drug Class Insights

The drug classes include PD-1/PD-L1 inhibitor, T cell activator, Immune activators, Fc fusion protein, and others.

PD-1 inhibitors have emerged as an important therapeutic class in the management of OPSCC, particularly in recurrent or metastatic disease. By blocking the PD-1 receptor on T cells, these agents prevent interaction with its ligands PD-L1 and PD-L2 expressed on tumor cells and within the tumor microenvironment, thereby restoring antitumor immune activity and overcoming immune evasion. KEYTRUDA and OPDIVO are the two leading PD-1 inhibitors studied extensively in OPSCC, with demonstrated clinical benefit in patients whose disease progressed after platinum-based therapy as well as in biomarker-selected frontline settings. Their mechanism-driven ability to reinvigorate cytotoxic T-cell responses has positioned PD-1 inhibitors as a backbone of immunotherapy in OPSCC, often considered in combination or sequencing strategies to further optimize outcomes.

Oropharyngeal Cancer Market Outlook

The current treatment market for HPV-positive oropharyngeal cancer is anchored by surgery and radiation, with CRT remaining central in advanced-stage management. In early-stage disease, TORS and precision radiation techniques such as IMRT are widely used, with adjuvant CRT applied when high-risk features are identified. Although there is ongoing interest in treatment de-intensification, present practice still prioritizes established CRT regimens and conventional surgical pathways to ensure durable disease control. In the recurrent and metastatic setting, immunotherapy dominates. KEYTRUDA is firmly established as first-line therapy, used either alone in PD-L1-positive patients or in combination with chemotherapy, while OPDIVO is standard following platinum-based failure. Cetuximab remains relevant for cisplatin-ineligible patients, primarily in combination with radiotherapy. A major recent shift has been the approval of perioperative KEYTRUDA for resectable locally advanced head and neck cancers, immediately expanding immunotherapy use into earlier disease stages and directly shaping HPV-driven cases. The present market therefore reflects a solid foundation of CRT and surgery, complemented by the rapid integration of KEYTRUDA, OPDIVO, and advanced RT delivery techniques.

• KEYTRUDA and OPDIVO are the primary PD-1 inhibitors approved for treating recurrent or metastatic (R/M) HNSCC.
• Currently, a number of HPV-targeted vaccines in HNSCC are being studied; the most encouraging findings have been seen when used in combination with checkpoint inhibitors as a first-line treatment for recurrent or metastatic disease. Although there are some studies looking at these vaccines in treatment-refractory patients, the response rate in that population tends to be lower. Additionally, ongoing trials are investigating the use of therapeutic vaccines without immunotherapy.
• Versamune HPV doublet (Versamune HPV + KEYTRUDA) and triplet regimen (Versamune HPV + PDS01ADC + Bintrafusp alfa) continue to show efficacy. Both doublet and triplet are expected to change the landscape of HPV16+ HNSCC.
• Although PD-1 inhibitors have reshaped the therapeutic landscape, their efficacy remains constrained by resistance mechanisms, including immunosuppressive tumor microenvironments and immune escape pathways. These limitations are particularly evident in patients with low PD-L1 expression or prior chemotherapy exposure.

HPV+ Oropharyngeal Cancer Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2025-2034. The landscape of HPV+ oropharyngeal cancer treatment has experienced a profound transformation with the uptake of novel drugs. These innovative therapies are redefining standards of care. Furthermore, the increased uptake of these transformative drugs is a testament to the unwavering dedication of physicians, oncology professionals, and the entire healthcare community in their tireless pursuit of advancing cancer care. This momentous shift in treatment paradigms is a testament to the power of research, collaboration, and human resilience.

HPV+ Oropharyngeal Cancer Pipeline Development Activities

The report provides insights into therapeutic candidates in Phase III, Phase II, and Phase I/II. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for HPV+ oropharyngeal cancer emerging therapy.

KOL Views

To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on HPV+ oropharyngeal cancer evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including oncologists, radiation oncologists, surgical oncologists, and others.

Delveinsight's analysts connected with 15+ KOLs to gather insights; however, interviews were conducted with 7+ KOLs in the 7MM. Centers such as MD Anderson Cancer Center, Jena University Hospital, University College London, Cambridge University, Yale University, International Agency for Research on Cancer, Carnegie Mellon University, University of Arizona, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns of HPV+ oropharyngeal cancer market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of gaps in disease diagnosis, patient awareness, physician acceptability, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided.

Conjoint Analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in event- free survival, one of the most crucial primary outcome measures is event-free survival and overall survival.

Further, the therapies' safety is evaluated, wherein the acceptability, tolerability, and adverse events are majorly observed, and this clearly explains the drugs side effects in the trials. In addition, the scoring is also based on the probability of success and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

Reimbursement may be referred to as the negotiation of a price between a manufacturer and payer that allows the manufacturer access to the market. It is provided to reduce the high costs and make the essential drugs affordable. Health technology assessment (HTA) plays an important role in reimbursement decision-making and recommending the use of a drug. These recommendations vary widely throughout the seven major markets, even for the same drug. In the US healthcare system, both Public and Private health insurance coverage are included. Also, Medicare and Medicaid are the largest government-funded programs in the US. The major healthcare programs including Medicare, Medicaid, Health Insurance Program (CHIP), and the state and federal health insurance marketplaces are overseen by the Centers for Medicare & Medicaid Services (CMS). Other than these, Pharmacy Benefit Managers (PBMs), and third-party organizations that provide services, and educational programs to aid patients are also present.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of currently used therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of HPV+ oropharyngeal cancer, explaining its causes, signs, symptoms, pathogenesis, and currently used therapies.
• Comprehensive insight into the epidemiology segments and forecasts, disease progression, and treatment guidelines has been provided.
• Additionally, an all-inclusive account of the emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current treatment landscape.
• A detailed review of the HPV+ oropharyngeal cancer market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis and expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM HPV+ oropharyngeal cancer market.

HPV+ Oropharyngeal Cancer Report Insights

• Patient Population
• Therapeutic Approaches
• HPV+ Oropharyngeal Cancer Pipeline Analysis
• HPV+ Oropharyngeal Cancer Market Size and Trends
• Existing and Future Market Opportunity

HPV+ Oropharyngeal Cancer Report Key Strengths

• 10 Years Forecast
• The 7MM Coverage
• HPV+ Oropharyngeal Cancer Epidemiology Segmentation
• Key Cross Competition
• Drugs Uptake and Key Market Forecast Assumptions

HPV+ Oropharyngeal Cancer Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT Analysis and Conjoint Analysis)

FAQs:

• What was the HPV+ oropharyngeal cancer market size, the market size by therapies, market share (%) distribution in 2024, and what would it look like by 2034? What are the contributing factors for this growth?
• What are the pricing variations among different geographies for approved therapies?
• What can be the future treatment paradigm of HPV+ oropharyngeal cancer?
• What are the disease risks, burdens, and unmet needs of HPV+ oropharyngeal cancer? What will be the growth opportunities across the 7MM concerning the patient population with HPV+ oropharyngeal cancer?
• What are the current options for the treatment of HPV+ oropharyngeal cancer? What are the current guidelines for treating HPV+ oropharyngeal cancer in the US, Europe, and Japan?
• What are the recent novel therapies, targets, mechanisms of action, and technologies being developed to overcome the limitations of existing therapies?

Reasons to Buy:

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the HPV+ oropharyngeal cancer market.
• Insights on patient burden/disease prevalence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the Analyst view section to provide visibility around leading classes.
• Highlights of access and reimbursement policies of current therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.