Head and Neck Squamous Cell Carcinoma - Market Insight, Epidemiology, and Market Forecast - 2034

Key Highlights:

• KEYTRUDA and OPDIVO are the primary PD-1 inhibitors approved for treating recurrent or metastatic (R/M) HNSCC.
• Over half of head and neck cancer patients relapse or metastasize despite multimodal treatment, reflecting the high prevalence of therapeutic resistance and underscoring the urgent need for more effective, tolerable targeted therapies to improve outcomes.
• The established efficacy of immune checkpoint inhibitors in recurrent and metastatic HNSCC has sparked a growing interest in their neoadjuvant use. Neoadjuvant immunotherapy in HNSCC is promising, as it may reduce the risk of local recurrence and distant metastasis, potentially improving overall survival.
• In HNSCC, radiotherapy remains a cornerstone of treatment, yet its curative potential is often undermined by radioresistance driven by aberrant activation of pathways such as PI3K/AKT/mTOR, EGFR, VEGF, FGFR, MEK/ERK, MET, CDK4/6, and Notch. Therapeutic inhibition of these signaling networks is emerging as a rational strategy to overcome resistance and enhance treatment efficacy.
• Therapeutic vaccination in HNSCC has gained significant momentum in recent years, with several strategies nearing clinical application.
• 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.
• Key players in the market include include: Merck (KEYTRUDA), Bristol Myers Squibb (OPDIVO), Coherus BioSciences (LOQTORZI), Immutep (Efti), Merus N.V. (Petosemtamab), NANOBIOTIX and Johnson & Johnson (HENSIFY, JNJ-1900, NBTXR3), PDS Biotechnology (Versamune HPV), and others.

DelveInsight's "Head and Neck Squamous Cell Carcinoma (HNSCC) - Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of HNSCC, historical and forecasted epidemiology as well as HNSCC market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The HNSCC market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM HNSCC market size from 2020 to 2034. The report also covers current HNSCC 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

Head and Neck Squamous Cell Carcinoma (HNSCC): Understanding and Treatment Algorithm

HNSCC Overview

HNSCC comprises a group of malignancies originating from the squamous cells lining the head and neck region, including the oral cavity, hypopharynx, nasopharynx, oropharynx, lip, nasal cavity, paranasal sinuses, and salivary glands. These structures play essential roles in respiration, swallowing, and conditioning inspired air by filtering and humidifying it. HNSCC represents a significant global health burden, with incidence and mortality rates showing considerable variation across geographic regions and demographic groups. The disease is more prevalent in certain populations, particularly men, older adults, and individuals of lower socioeconomic status..

HNSCC Diagnosis

Diagnosis of HNSCC is confirmed by biopsy of the primary tumor or neck mass, with the approach depending on lesion location, primary tumors are usually sampled with cup forceps, incisional, or excisional biopsy, while suspicious cervical lymph nodes undergo fine-needle aspiration (FNA); excisional neck mass biopsy is avoided unless FNA is repeatedly non-diagnostic, no primary is found, or lymphoma is suspected. Histopathology shows varying degrees of squamous differentiation, from well-differentiated tumors with keratin pearls to poorly differentiated tumors with pleomorphism and minimal keratinization; HPV-negative cases are often well or moderately differentiated, whereas HPV-positive tumors tend to be poorly differentiated or basaloid. Diagnosis is typically made with hematoxylin and eosin staining, with immunohistochemistry for pancytokeratin, cytokeratin 5/6, and p63 used for poorly differentiated cases. HPV testing is mandatory for all oropharyngeal and unknown primary tumors, with p16^INK4A^ immunohistochemistry (positive if >70% diffuse staining) serving as the standard surrogate marker for HPV status.

Head and Neck Squamous Cell Carcinoma (HNSCC) Treatment

HNSCC requires a multidisciplinary approach. In locally or regionally advanced disease, surgery and/or radiation remain the mainstays, with platinum-based chemotherapy used as induction, concurrent, or adjuvant therapy. In the relapsed/metastatic setting, outcomes have improved with biologics and immune checkpoint inhibitors. Pembrolizumab, alone for PD-L1-positive tumors or with chemotherapy for broader eligibility-is standard first-line therapy, offering chemotherapy-free options for select patients. Response rates improve when chemotherapy is added, especially in HPV-positive tumors, which tend to have better prognosis and may present with oligometastatic disease suitable for local ablation or resection.

Targeted approaches, including EGFR inhibitors, PI3K/AKT/mTOR pathway inhibitors, and antiangiogenic agents, are under active investigation, alongside HPV-specific vaccines, antibody-drug conjugates, and cellular therapies. Novel strategies aim to overcome resistance and enhance immune response, including modulation of the tumor microenvironment, synthetic lethality for tumor suppressor loss, and targeting aberrant methylation. These developments hold promise for further improving survival and disease control in HNSCC.

Head and Neck Squamous Cell Carcinoma (HNSCC): Epidemiology

The HNSCC 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, site-specific incident cases of HNSCC, HPV+ status-specific incident cases of HNSCC, stage-specific incident cases of HNSCC and total treated cases of HNSCC in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2020 to 2034.

• Among the 7MM, the US accounted for maximum cases of head and neck cancer with about 71,000. In head and neck cancer, approximately 90% of cases are classified as head and neck squamous cell carcinoma (HNSCC).
• Among EU4 and the UK, site-specific cases of HNSCC were found maximum in the oral cavity.
• Germany accounted for about 2,700 OPSCC incident cases in 2024.
• Japan accounted for about 30,000 cases of HPV16+ OPSCC incident cases in 2024.

Head and Neck Squamous Cell Carcinoma (HNSCC) Drug Chapters

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

Marketed Drugs

KEYTRUDA (pembrolizumab): Merck

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 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

In June 2025, the FDA approved KEYTRUDA for adults with resectable locally advanced HNSCC whose tumors express PD-L1, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy with or without cisplatin after surgery, and then as a single agent. This is the first approval for HNSCC in 6 years and the first overall perioperative approval for locally advanced HNSCC.

OPDIVO (nivolumab): Bristol Myers Squibb (BMS)

OPDIVO is a 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.

In June 2025, BMS presented Phase III NIVOPOSTOP trial results at ASCO 2025, showing adjuvant nivolumab with cisplatin and radiotherapy improved 3-year DFS in high-risk LA-SCCHN patients, showing potential as a new standard treatment.

Emerging Drugs

Efti (eftilagimod alfa): Immutep/ Merck

Efti is a soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, Efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system's ability to fight cancer. Efti has Fast Track designation in 1L HNSCC.

In August 2025, Immutep announced it has received positive and constructive feedback from the US FDA, regarding future clinical development of its first-in-class MHC Class II agonist, efti in combination with KEYTRUDA, for first line treatment of recurrent/metastatic 1L HNSCC patients who have PD-L1 expression below 1 (Combined Positive Score [CPS] <1).

Petosemtamab (MCLA-158): Merus N.V.

Petosemtamab, or MCLA-158, is a Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity. Petosemtamab has also received FTD and BTD from US FDA.

In August 2025,Merus announced LiGeR-HN1 Phase III trial in 1L R/M HNSCC and LiGeR-HN2 Phase III trial in 2/3L r/m HNSCC are enrolling, with both trials expected to be substantially enrolled by 2025 and potential top line interim readout for one or both trials in 2026.

Drug Class Insights

The drug classes include PD-1 inhibitors, APC activator, dual EGFR/LRG5 inhibitor, T cell activator, E6 and E7 modulators, Immunostimulants, IL-2 inhibitor, and others.

PD-1 inhibitors are immune checkpoint blockade therapies that restore antitumor immune surveillance by blocking the interaction between the PD-1 receptor and its PD-L1/PD-L2 ligands, thereby reinvigorating T-cell activity. In HNSCC, KEYTRUDA and OPDIVO have reshaped treatment paradigms for recurrent or metastatic disease, shifting focus from short-lived responses with chemotherapy to the potential for durable disease control. Their clinical impact is particularly notable in biomarker-selected populations, where PD-L1 expression can guide therapy, underscoring the growing role of precision immuno-oncology in HNSCC management.

Head and Neck Squamous Cell Carcinoma (HNSCC) Market Outlook

The HNSCC market is consolidating around a core group of approved immunotherapies that are redefining treatment sequencing and patient selection strategies. In the R/M HNSCC segment, KEYTRUDA (pembrolizumab) and OPDIVO, OPDIVO QVANTIG (nivolumab) have become standard-of-care options, with adoption driven by PD-L1 biomarker testing and evolving guideline criteria. CETUXIMAB retains value in locally advanced disease in combination with radiation, as well as in select metastatic cases. Overall, the market is transitioning toward a precision-based model in which immunotherapy serves as the backbone of care across multiple head and neck malignancies, integrated earlier in treatment algorithms to improve survival outcomes.

Head and Neck Squamous Cell Carcinoma (HNSCC) 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 HNSCC 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.

Key Highlights:

• In August 2025, Coherus Oncology announced that the National Comprehensive Cancer Network (NCCN) had revised its guidelines to grant LOQTORZI preferred status for the NPC indication.
• In June 2025, PDS Biotech announced updated positive data from the VERSATILE-002 trial and additional trials evaluating Versamune HPV to treat head and neck cancers at the 2025 ASCO annual meeting.
• In May 2025, Coherus BioSciences announced a clinical collaboration with STORM Therapeutics, to evaluate STC-15, a METTL3 inhibitor, in combination with LOQTORZI, a next-generation PD-1 inhibitor, in a Phase Ib/II study for the treatment of NSCLC, HNSCC, melanoma and endometrial cancer.
• In April 2025, the US FDA approved penpulimab-kcqx (Akeso Biopharma) with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing NPC. FDA also approved penpulimab-kcqx as a single agent for adults with metastatic non-keratinizing NPC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

Head and Neck Squamous Cell Carcinoma (HNSCC) 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 HNSCC 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 HNSCC 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 - Dana-Farber Cancer Institute, Allina Health Cancer Institute, Memorial Sloan Kettering Cancer Center, Winship Cancer Institute of Emory University, University of Tokyo, European Institute of Oncology, University of Birmingham, American Association for Cancer Research, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or HNSCC 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 HNSCC, 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 HNSCC 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 HNSCC market.

Head and Neck Squamous Cell Carcinoma (HNSCC) Report Insights

• Patient Population
• Therapeutic Approaches
• HNSCC Pipeline Analysis
• HNSCC Market Size and Trends
• Existing and Future Market Opportunity

Head and Neck Squamous Cell Carcinoma (HNSCC) Report Key Strengths

• 10 Years Forecast
• The 7MM Coverage
• HNSCC Epidemiology Segmentation
• Key Cross Competition
• Drugs Uptake and Key Market Forecast Assumptions

Head and Neck Squamous Cell Carcinoma (HNSCC) Report Assessment

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

FAQs:

• What was the HNSCC 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 HNSCC?
• What are the disease risks, burdens, and unmet needs of HNSCC? What will be the growth opportunities across the 7MM concerning the patient population with HNSCC?
• What are the current options for the treatment of HNSCC? What are the current guidelines for treating HNSCC 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 HNSCC 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.